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Bioinorganic Chemistry Na K Cl Overview • Potassium, sodium and chloride are major electrolytes in living organisms. • Potassium is abundant in the cell. • Sodium is abundant in the extracellular fluids. • The major counter-ion is chloride. Bioinorganic Chemistry Na K Cl Sodium and potassium The trans-membrane sodium-potassium gradient is maintained by the Na+/K+ATPase ion pump which transfers 3 Na+ into extracellular space while letting in 2 K+ ions. Bioinorganic Chemistry Na K Cl Directional selectivity The Na+/K+-ATPase ion pump uses the same concepts that makes crown ethers and cryptand ligands selective for certain cations: • The selective ligand (ionophore) must provide hard binding sites for alkali and alkaline earth metal ions, mainly carboxylates. • The donor array must be rigid such that only the desired ion type is bound tightly according to its radius. • The real achievement in Na+/K+-ATPase is that the selective binding sites can be switched from Na+ to K+ and back by conformational changes. Bioinorganic Chemistry Na K Cl Crowns and cryptands Bioinorganic Chemistry Na K Cl K+ channel Bioinorganic Chemistry Na K Cl Bioelectricity The asymmetric ion exchange causes a trans-membrane potential. Muscle and nerve cells keep up a high potential difference by this mechanism. One molecule of ATP is consumed during a transport cycle. Typical resting potentials: skeletal muscle -95 mV, smooth muscle -50 mV The Na+/K+ gradient can be temporarily lowered by opening passive ion channels. The channel opening is triggered, depending on the type, by messengers or an electric potential. In the case of electric triggering, a wave of gradient breakdown propagates along the membrane: the action potential Bioinorganic Chemistry Na K Cl Action potential Bioinorganic Chemistry Na K Cl Nutrient transport The trans-membrane sodium gradient provides the energy for trans-membrane transport proteins which import glucose, amino acids and other “raw material” into the cell. Example: Some renal epithelial cells extract Na+ and glucose together from the fresh urine filtrate. The Na+ gradient provides the energy to drive the process. Bioinorganic Chemistry Na K Cl Osmotic control Cells contain huge amounts of immobile electrolyte: proteins Proteins: mainly anionic Cations accumulate with proteins, and they bind water very efficiently: the cell starts to swell. Pumping out excess cations helps to remove water, swelling is limited. Bioinorganic Chemistry Na K Cl Chloride Chloride has to be co-transferred with sodium to produce secretions like sweat or saliva. Therefore, ion channels which allow for passive Cl- transfer exist in cell membranes. The channels are turned on and off by messengers. Closed channels limit the sodium gradient that can be built up across the membrane. Genetic defects of chloride channels cause severe diseases.